The goal of this proposal is to develop methods for the early detection of hepatocellular carcinoma (HCC) and hepatitis. The hypothesis that changes in the amount or modification of serum polypeptides correlate with the onset of HCC or hepatitis will be determined. Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of HCC and hepatitis, with disease progression occurring after many years. Serum polypeptides from individuals at different stages in the disease continuum will be resolved by "Proteomic" 2-dimensional gel analysis. Our preliminary evidence and the work of others demonstrate that 2D gel technology has advanced to the point where expressed protein profiles of biological samples can be reproducibly resolved. Polypeptides that correlate (by their appearance, disappearance or post translational modification) with disease status will be identified. Correlating polypeptides will be characterized by a variety of methods available to us: data base reference, immunological methods or micro sequencing. Identification of biomarkers that help in the diagnosis and prediction of liver disease in this high-risk population will have enormous public health benefit, given the limitations on current methods. It will also provide insights about the mechanisms of progression of this disease family and offer a platform technology for the use of proteome diagnostics in other areas of cancer detection and liver decompensation.